Nature Medicine
9, 796 - 800 (2003)
Published online: 18 May 2003; | doi:10.1038/nm879
Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generationEdward Brown1, 5, Trevor McKee3, 5, Emmanuelle diTomaso1, Alain Pluen4, Brian Seed2, Yves Boucher1
& Rakesh K. Jain11
Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. 2
Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. 3
Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. 4
School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester M139PL, UK. 5
These authors contributed equally to this work.
Correspondence should be addressed to Rakesh K. Jain jain@steele.mgh.harvard.eduThe content and structure of collagen is essential in governing the delivery of therapeutic molecules in tumors. Thus, simple histological staining of tumor tissue biopsies for collagen could be used to assess the accessibility of molecular therapeutics in tumors. Here we show that it is possible to optically image fibrillar collagen in tumors growing in mice using second-harmonic generation (SHG). Using this noninvasive technique, we estimated relative diffusive hindrance, quantified the dynamics of collagen modification after pharmacologic intervention and provided mechanistic insight into improved diffusive transport induced by the hormone relaxin. This technology could offer basic scientists and clinicians an enhanced ability to estimate the relative penetrabilities of molecular therapeutics.
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